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Purpose: Understanding pulmonary artery (PA) branches and their variations is crucial for successful lung resection. We aimed to evaluate the segmental PA branching pattern of the left upper lobe (LUL) using thin-section computed tomography (TSCT) images and 3D-CT angiography (3D-CTA)., Materials and Methods: This study included 108 patients who underwent CTA and left upper lobectomy. The segmental PA branching pattern of the LUL was meticulously identified by two thoracic radiologists using 3D-CTA and TSCT images. The lingular artery branches from the left PA (LPA) were classified into mediastinal type (pars mediastinalis: PM), interlobar type (pars interlobaris: PI), and PI originating from the lower portion (PI'), specifically from A8. The intraoperative findings of the PA branches of the LUL were compared with the preoperatively obtained 3D-CTA and TSCT images in each patient's case., Results: The median (range) number of LPA branches of the LUL was 4.36 (3-8). The most common number of A1 + 2 branches was two, seen in 34 cases (31.5%). One or more branches of A1 + 2c directly originating from the LPA were found in 63 cases (58.3%). The number of branches of A3 was single in 85 cases and the most frequent (78.7%). Instances where one or more branches of A3a directly originated from the LPA were found in seven cases (6.5%). A1 + 2 and A3 origins were separate and independent in 40 cases (37.0%). As the branching pattern of the lingular artery, PI/PI' was most frequent (61.1%). PI´ was observed in 26 cases (24.1%). Inter-observer agreement for A1 + 2, A1 + 2c, A3, A3a, and lingular artery branching patterns was moderate to substantial (κ = 0.53-0.72). Preoperative 3D-CTA and TSCT images identified 99.8% of LPA branches compared to intraoperative findings, except one., Conclusion: The segmental PA branching pattern of the LUL can be evaluated using TSCT and 3D-CTA images, providing precise preoperative information., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest relevant to the content of this article. Ethics approval: This study was conducted in accordance with the principles of the Declaration of Helsinki. This study was approved by the Institutional Review Board (approval number: 2024-017). Informed consent: The need for informed consent was waived due to the retrospective nature of this study., (© 2024. The Author(s).)

In an 81-year-old man, brain diffusion-weighted MRI revealed punctate high-intensity lesions in the bilateral frontal cortex. Three months later, these lesions had extended into the cerebral cortices. Six months after the original MRI, the patient developed cognitive decline. Clinically, he appeared to have Creutzfeldt-Jakob disease (CJD) based on brain MRI and cerebrospinal fluid examination findings. We identified a compound heterozygous mutation (V180I/M232R) in PRNP and diagnosed him with genetic CJD. This case of CJD with a compound heterozygous PRNP mutation had a relatively old onset, slowly progressive course, and low frequency of periodic synchronous discharges. Additionally, we detected CJD-associated brain MRI abnormalities before symptom onset. Reports of presymptomatic CJD such as the present case are important for the development of new therapeutic agents for CJD.

Background: According to the gene-environment interactions concept, the mechanism of health impairment can be explained by genetic factors, environmental factors, or their interaction. Physical and mental health effects resulting from environmental exposure may be classified either as toxicity, immune response, and allergic reaction. Moreover, despite the already established therapeutic approaches to bronchial asthma and decreasing mortality due to bronchial asthma, patients with difficult and severe asthma are increasing in number. This review outlines recent topics in the field of allergies, focusing on asthma., Results and Discussion: Living environment-derived pollutants and their involvement in the pathogenesis of asthma and its exacerbation, referred to here as an exposome concept, comprises the three domains of internal, specific external, and general external. Living environment-derived pollutants include exposure to pollutants in workplaces, climate change, air pollution, microplastics, tobacco smoke, biodiversity change and loss, changing dietary habits, and the microbiome. These are associated with the modernization, urbanization, and globalization of human society. Although many novel compounds are currently available, their harmful health effects, such as allergy, are not thoroughly understood. Hence, the means to mitigate these are unknown. Dietary changes from a traditional diet rich in fish to a Western-style diet are considered critical environmental factors and therefore, associated with an increased prevalence of allergies. Cytokines, including thymic stromal lymphopoietin, IL-25, and IL-33, released from the airway epithelium in response to various triggers (exposure to diverse environmental factors) are known as alarmins. Anti-alarmin antibodies are a promising therapeutic approach against severe and difficult allergic disorders. Collaboration between hospitals and clinics and occupational and clinical medicine is imperative for treating and managing severe asthma. In addition to avoiding environmental exposure, understanding the pathogenesis and exacerbation of asthma is essential for future research in the field of allergy and immunotoxicology.

Introduction: Despite improved hearing, children who receive cochlear implants (CIs) at a later age encounter difficulties in adapting to society, exposing them to psychological and social risks. This study contributes to the conceptualisation of preventive interventions in schools to address potential issues so that these children can play a more active role in society., Methods: A total of 52 children (aged 3-12 years) who received CIs at 30 months of age were assessed using the Asahide-Shiki Social Adaptive skills test, which evaluates children's social skills on four domains: (A) language, (B) everyday life, (C) social life, (D) communication., Results: Overall, the average score of children who receive CIs at a later age was lower than that of their hearing peers. Pre-school children obtained statistically lower scores in all skills. While this general lag in skill development was no longer observed in the lower grades of elementary school, the upper-grade school children presented lower scores than their hearing peers, although only those pertaining to everyday and social life skills were statistically significant. Accordingly, the average scores were distributed in an inverted V shape among age groups., Conclusion: These results suggest that children who receive CIs at a later age develop their social skills later than their peers with normal hearing in preschool, catch up to their peers in the 1st to 3rd grades, and then lag in the 4th to 6th grades. Accordingly, acquiring age-appropriate social skills in the upper grades remains a challenge for children who obtained CIs at the age of approximately 3, suggesting the need for intervention programs for school-age children even when they do not show significant language acquisition delays., (S. Karger AG, Basel.)

This study aimed to investigate the release of metallic ions from cobalt-chromium (Co-Cr) alloys fabricated by additive manufacturing (AM) for comparison with dental casting. Co-Cr alloys were fabricated via AM using selective laser melting (SLM) and electron beam melting (EBM) in powder-bed fusion. Polished and mechanically ground specimens were prepared. Each specimen was analyzed using an electron probe microanalyzer (EPMA). Each specimen was immersed in an acidic saline solution for 7 days in accordance with ISO 10271: 2020. The EPMA indicated the segregation of some elements in the as-prepared SLM and EBM specimens, whereas the polished and ground specimens exhibited a homogenous elemental distribution. The total amount of ion release from the SLM and EBM specimens was confirmed to be less than 7 μg/cm 2 , which was less than 42 μg/cm 2 for the cast specimen. The polished and ground specimens exhibited an even lower ion release than the as-prepared specimens. The amount of ions released from the Co-Cr alloy was less than the 200 μg/cm² requirement of ISO 22674: 2022. Co-Cr alloys fabricated by SLM and EBM could provide superior corrosion resistance to cast specimens. AM could be a valuable method for fabricating appliances and denture frameworks in dentistry.

The circadian clock protein reverse erythroblastosis virus (REV)-ERBα is implicated in the pathogenesis of various diseases, including cancer and myocardial infarction. Emerging evidence suggests that SR9009, an agonist of REV-ERBα, regulates multiple signaling molecules independent or dependent of REV-ERBα. However, the impact of SR9009 on renal fibrosis remains largely unevaluated. In this study, we investigated the effects of SR9009 on transforming growth factor (TGF)-β1-induced fibrotic responses and elucidated the mechanisms involved. Masson's trichome staining revealed that in the unilateral ureteral obstruction groups, there was a decrease in REV-ERBα expression, accompanied by increased levels of the profibrotic factor TGF-β1 and the fibrosis marker α-smooth muscle actin (α-SMA). REV-ERBα knockdown significantly increased α-SMA expression in NRK-49F cells. SR9009 significantly attenuated unilateral ureteral obstruction-induced fibrosis and TGF-β1-induced fibrotic responses in normal rat kidney fibroblasts (NRK-49F cells). Conversely, the REV-ERBα antagonist SR8278 did not affect TGF-β1-induced fibrotic responses. Mechanistic studies revealed that SR9009 significantly inhibited the phosphorylation of ERK and p38, concomitant with reduced α-SMA levels, suppressing TGF-β1-induced NADPH oxidase 4 (NOX4) mRNA expression in NRK-49F cells. Notably, SR9009 did not influence the expression of dual specificity phosphatase 4, which dephosphorylates MAPKs, including p38. Furthermore, REV-ERBα knockdown did not affect the ability of SR9009 to inhibit TGF-β1-induced fibrotic responses and NOX4 expression in NRK-49F cells. In conclusion, SR9009 exerts a protective role against renal fibrosis independent of REV-ERBα. Therefore, SR9009 is a promising therapeutic agent for the prevention and treatment of renal fibrosis associated with renal failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The transcription factor brain and muscle Arnt-like protein-1 (BMAL1) is a clock protein involved in various diseases, including atherosclerosis and cancer. However, BMAL1's involvement in kidney fibrosis and the underlying mechanisms remain largely unknown, a gap addressed in this study. Analysis through Masson's trichrome and Sirius red staining revealed that all groups exposed to unilateral ureteral obstruction showed increased BMAL1 protein expression accompanied by increased TGF-β1 expression and elevated key fibrosis markers, including α-SMA, compared with sham groups. Although TGF-β1 induced BMAL1 protein expression accompanied by increased α-SMA expression in NRK-49F cells, the REV-ERBα agonist GSK4112, a transcriptional repressor of BMAL1, or siRNA targeting BMAL1 significantly inhibited TGF-β1-induced α-SMA expression. Furthermore, BMAL1 knockdown significantly suppressed TGF-β1-induced NOX4/ROS/p38 pathways in NRK-49F cells. Thus, BMAL1 positively regulates TGF-β1-induced signaling associated with fibrotic responses via the NOX4/ROS/p38 pathway. Overall, this study uncovers BMAL1 as a promising therapeutic target for preventing and treating kidney fibrosis, potentially preventing renal failure., (© 2025 International Federation of Cell Biology.)

Objectives: Temporomandibular joint (TMJ) osteoarthritis (OA) is an inflammatory disease that involves periarthritis of the TMJ and destruction of cartilage tissue in the mandibular condyle. However, the role of proinflammatory cytokines in the expression levels of matrix metalloproteinase (MMP) remains inconclusive. Thus, in this study, we aimed to investigate the effect of proinflammatory cytokines on the expression of MMPs., Methods: FLS1 cells (mouse TMJ-derived synovial cell line) were treated with tumor necrosis factor alpha (TNF-α) or interleukin (IL)-1β in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors. The mRNA expression levels of MMP-2 and MMP-9 were examined by reverse transcription-quantitative polymerase chain reaction. Additionally, the phosphorylation status of extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK in the FLS1 cells treated with TNF-α or IL-1β was evaluated by performing western blotting analysis., Results: TNF-α and IL-1β significantly increased the expression of MMP-9 in the FLS1 cells; however, MMP-2 expression remained unaffected. Mitogen-activated protein kinase kinase (MEK) and p38 MAPK inhibitors significantly suppressed cytokine-induced MMP-9 upregulation. Conversely, Jun amino-terminal kinase (JNK) inhibitors further increased MMP-9 expression in the cells treated with TNF-α or IL-1β. Moreover, TNF-α and IL-1β enhanced ERK1/2 and p38 MAPK phosphorylation in the FLS1 cells., Conclusions: TNF-α and IL-1β induced MMP-9 expression in the FLS1 cells via the MEK/ERK and p38 MAPK pathways and suppressed it via the JNK pathway. Thus, proinflammatory cytokines control MMP-9 expression in TMJ-OA by regulating multiple MAPK pathways., Competing Interests: Declaration of Competing Interest All authors are required to disclose any COI within the period of 12 months prior to the submission of any manuscript in the subject matter of which any company, entity, or organization has an interest. The corresponding author is required to complete this form with information from all the authors listed in the manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Allicin (diallyl thiosulfinate) is an abundant bioactive compound in garlic (Allium sativum L.) with broad-spectrum antiinflammatory, antifungal, antioxidant, and antitumor properties. The bioactive compounds of garlic including allicin may also help reduce the incidence of various diseases, although the individual contributions and precise mechanisms are still largely unknown. In this study, we reveal that allicin and the closely related compounds diallyl disulfide and diallyl trisulfide (all containing more than one disulfide bond) protect mouse hippocampal HT22 cells against chemically induced ferroptosis, a newly defined form of cell death characterized by iron-dependent lipid peroxidation. In contrast, these organosulfur compounds did not prevent chemically induced apoptosis. The antiferroptotic efficacies of these compounds were strongly associated with prevention of lipid peroxidation and reactive oxygen species production but independent of glutathione upregulation, ferrous iron chelation, and modulation of the nuclear factor erythroid 2 (NF-E2)-related factor-2-antioxidant element response pathway. Additional studies are warranted on the therapeutic potential of allicin and related compounds in garlic for neurodegenerative diseases associated with ferroptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Medical advances in intensive care units (ICUs) have resulted in the emergence of a new patient population-those who survive the initial acute phase of critical illness, but require prolonged ICU stays and develop chronic critical symptoms. This condition, often termed Persistent Critical Illness (PerCI) or Chronic Critical Illness (CCI), remains poorly understood and inconsistently reported across studies, resulting in a lack of clinical practice use. This scoping review aims to systematically review and synthesize the existing literature on PerCI/CCI, with a focus on definitions, epidemiology, and outcomes for its translation to clinical practice., Methods: A scoping review was conducted using MEDLINE and Scopus, adhering to the PRISMA-ScR guidelines. Peer-reviewed original research articles published until May 31, 2024 that described adult PerCI/CCI in their definitions of patient populations, covariates, and outcomes were included. Data on definitions, epidemiology, and outcomes were extracted by a data charting process from eligible studies and synthesized., Results: Ninety-nine studies met the inclusion criteria. Of these studies, 64 used the term CCI, 18 used PerCI, and 17 used other terms. CCI definitions showed greater variability, while PerCI definitions remained relatively consistent, with an ICU stay ≥ 14 days for CCI and ≥ 10 days for PerCI being the most common. A meta-analysis of the prevalence of PerCI/CCI among the denominators of "all ICU patients", "sepsis", "trauma", and "COVID-19" showed 11% (95% confidence interval 10-12%), 28% (22-34%), 24% (15-33%), and 35% (20-50%), respectively. A meta-analysis of in-hospital mortality was 27% (26-29%) and that of one-year mortality was 45% (32-58%). Meta-analyses of the prevalence of CCI and PerCI showed 17% (16-18%) and 18% (16-20%), respectively, and those for in-hospital mortality were 28% (26-30%) and 26% (24-29%), respectively. Functional outcomes were generally poor, with many survivors requiring long-term care., Conclusions: This scoping review synthesized many studies on PerCI/CCI, highlighting the serious impact of PerCI/CCI on patients' long-term outcomes. The results obtained underscore the need for consistent terminology with high-quality research for PerCI/CCI. The results obtained provide important information to be used in discussions with patients and families regarding prognosis and care options., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Prion diseases, including Creutzfeldt-Jakob disease (CJD), are deadly neurodegenerative disorders characterized by the buildup of abnormal prion proteins in the brain. This accumulation disrupts neuronal functions, leading to the rapid onset of psychiatric symptoms, ataxia, and cognitive decline. The urgency of timely diagnosis for effective treatment necessitates the identification of strongly correlated biomarkers in bodily fluids, which makes our research crucial. In this study, we employed a fully automated multiplex ELISA (Ella ® ) to measure the concentrations of 14-3-3 protein, total tau protein, and neurofilament light chain (NF-L) in cerebrospinal fluid (CSF) and serum samples from patients with prion disease and analyzed their link to disease prognosis. However, in North American and European cases, we did not confirm a correlation between NF-L levels and survival time. This discrepancy is believed to stem from differences in treatment policies and measurement methods between Japan and the United States. Nonetheless, our findings suggest that NF-L concentrations could be an early diagnostic marker for CJD patients with further enhancements. The potential impact of our findings on the early diagnosis of CJD patients is significant. Future research should focus on increasing the number of sCJD cases studied in Japan and gathering additional evidence using next-generation measurement techniques.

Most cases of dementia with Lewy bodies (DLB) follow a chronic course. However, some cases of rapidly progressive dementia (RPD) are difficult to distinguish from other diseases. Herein, we report how to differentiate DLB presenting with RPD from other diseases and its pathological features, with examples from our own experience. A 70-year-old man with RPD and psychiatric symptoms, including hallucinations and delusions, was transferred to our hospital. We suspected Creutzfeldt-Jakob disease (CJD), but disease-specific tests were all negative. The patient was treated with corticosteroids on the suspicion of an autoimmune condition; however, his symptoms did not improve. Based on the results of nuclear medicine and other tests, we suspected DLB and administered anti-Parkinsonian drugs; however, they were ineffective, and the patient died. Brain autopsy revealed extensive deposits of Lewy bodies, which were pathologically diagnosed as DLB. Additionally, extensive deposition of senile plaques was observed; however, neurofibrillary tangles (NFTs) were not prominent. DLB generally presents as a chronic disease. However, some patients with DLB present with RPD; therefore, the differential diagnosis of other diseases, such as CJD, is very important. In addition, although this case was not diagnosed with Alzheimer's disease (AD) due to the lack of NFTs, extensive amyloid deposition was observed in the brain tissue. Previous reports have described cases of RPD with amyloid deposition alone, and in this case too, it is suggested that amyloid deposition might have had a strong influence on the clinical course of RPD., (© 2024 Japanese Society of Neuropathology.)

Hyphal elongation is the vegetative growth of filamentous fungi, and many species continuously elongate their hyphal tips over long periods. The details of the mechanisms for maintaining continuous growth are not yet clear. A novel short lifespan mutant of N. crassa that ceases hyphal elongation early was screened and analyzed to better understand the mechanisms for maintaining hyphal elongation in filamentous fungi. The mutant strain also exhibited high sensitivity to mutagens such as hydroxyurea and ultraviolet radiation. Based on these observations, we named the novel mutant "mutagen sensitive and short lifespan 1 (ms1)". The mutation responsible for the short lifespan and mutagen sensitivity in the ms1 strain was identified in DNA polymerase γ (mip-1:NCU00276). This mutation changed the amino acid at position 814 in the polymerase domain from leucine to arginine (MIP-1 L814R). A dosage analysis by next generation sequencing (NGS) reads suggested that mitochondrial DNA (mtDNA) sequences are decreased non-uniformly throughout the genome of the ms1 strain. This observation was confirmed by quantitative PCR for three representative loci and restriction fragment length polymorphisms in purified mtDNA. Direct repeat-mediated deletions, which had been reported previously, were not detected in the mitochondrial genome by our whole-genome sequencing analysis. These results imply the presence of novel mechanisms to induce the non-uniform decrease in the mitochondrial genome by DNA polymerase γ mutation. Some potential reasons for the non-uniform distribution of the mitochondrial genome are discussed in relation to the molecular functions of DNA polymerase γ., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Diffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt-Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype., Case Presentation: A 72-year-old Japanese man developed a mild unsteady gait that had persisted for 1 year. DWI revealed isolated thalamic diffusion hyperintensities. Over the following 4 years, his condition progressed to include ataxia and cognitive decline. Repeated cerebrospinal fluid tests were negative for 14-3-3 protein, total tau protein, and real-time quaking-induced conversion assay. Electroencephalography did not show periodic sharp wave complexes or generalized periodic discharges. Despite these findings, thalamic DWI abnormalities persisted and evolved to include cortical lesions in the later stage of the disease. Genetic testing confirmed a 129MM genotype with no pathogenic PrP gene variants. Brain autopsy identified type 2 pathogenic PrP and the absence of the M2-thalamic prion strain, suggesting an MM2-cortical (MM2C)-subtype of sCJD. Histopathology revealed small vacuoles (sv) and patchy-perivacuolar PrP deposits without large vacuoles (lv). Patchy-perivacuolar deposits are a characteristic feature of the MM2C (lv) subtype and indicate MM2C (lv) pathology. Thus, this case was classified as a rare MM2C (sv + lv) subtype. No PrP protein staining was observed in the thalamus, despite spongiform changes with small vacuoles., Conclusions: This case underscores the diagnostic challenges of atypical CJD with isolated thalamic abnormalities on DWI. Despite negative cerebrospinal fluid findings and clinical diagnostic criteria, persistent DWI abnormalities and evolving clinical symptoms continued to raise suspicion of CJD. A definitive diagnosis, being the MM2C (sv + lv) subtype of sCJD, was confirmed upon pathological examination. Even when atypical findings, such as isolated thalamic abnormalities, are observed and various tests are negative, if suspicion of CJD cannot be ruled out, it is important to confirm the diagnosis and pathological subtypes via postmortem analysis., Competing Interests: Declarations. Ethics approval and consent to participate: Autopsy and gene analysis were performed after written informed consent was obtained from the family of the patient. The experimental protocol was approved by the Independent Review Board of Yokohama City University. All experiments were performed in accordance with institutional guidelines. Consent for publication: Written informed consent was obtained from the family for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Precise regulation of organ size and position is crucial for optimal organ function. Since the swim bladder is primarily responsible for buoyancy in teleosts, early development and subsequent inflation of the swim bladder should be appropriately controlled with the body growth. However, the underlying mechanism remains unclear. In this study, we show that the size and position of the swim bladder are physically constrained by the surrounding bones in zebrafish. Non-invasive micro-CT scanning revealed that the anterior edge of the swim bladder is largely attached to the os suspensorium, which is an ossicle extending medioventrally from the 4th centrum. Additionally, we observed that hoxc6a mutants, which lack the os suspensorium, exhibited an anterior projection of the swim bladder beyond the 4th vertebra. During the swim bladder development, we found that the counterclockwise rotation of the os suspensorium correlates with posterior regression of the swim bladder, suggesting that the os suspensorium pushes the swim bladder posteriorly into its proper position. Furthermore, our results revealed a close association between the posterior region of the swim bladder and the pleural ribs. In hoxaa cluster mutants with additional ribs, the swim bladder expanded posteriorly, accompanied by an enlarged body cavity. Taken together, our results demonstrate the importance of the surrounding bones in the robust regulation of swim bladder size and position in zebrafish., (© 2024 Anatomical Society.)

Introduction Delirium in the intensive care unit (ICU) significantly impacts patient outcomes. While family involvement may help prevent delirium in ICU patients, its effect during mechanical ventilation remains unclear. This study investigated the association between verbal communication during family visits and early post-extubation delirium in mechanically ventilated ICU patients. Materials and methods This retrospective, analytical observational study used data from the hospital's standard electronic health record (EHR) system, which includes routine medical and nursing documentation. We conducted this study in a 10-bed emergency ICU at an academic hospital in rural Japan from April 1, 2019, to December 31, 2020. We included patients aged ≥18 years who received invasive positive pressure ventilation for >48 hours. We excluded patients who were discharged while intubated, required a tracheostomy, or were unable to be assessed using the intensive care delirium screening checklist (ICDSC). The primary outcome was the maximum ICDSC score within 24 hours post-extubation. We conducted multiple regression analyses with ICDSC as the outcome. Results A total of 110 patients were analyzed. The mean age was 64.7 years (standard deviation ± 14.3), and 73 patients were male (66.4%). The median duration of intubation was five days (interquartile range (IQR), 4-8), and the median sequential organ failure assessment (SOFA) score was 8 (IQR, 6-11). The median ICDSC within 24 hours post-extubation was 3 (IQR, 2-5). Of the total 110 patients, 28 (25.5%) could communicate verbally. Patients who could communicate verbally had lower SOFA scores, longer duration of intubation, more frequent family visits, and higher intensive care mobility scale (IMS) scores during intubation. Neither single nor multiple regression showed a significant association between verbal communication and post-extubation ICDSC. Conclusions We did not find a statistically significant association between verbal communication during family visits with patients and ICDSC within 24 hours post-extubation. Potential confounders and variations in care practices may have influenced the results. Further studies are needed to address these limitations., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Committee of the Akita University Graduate School of Medicine issued approval 2951. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kudou et al.)

Background: Japanese dietary patterns have traditionally focused on vegetables, legumes, and fish; however, in the last few quarters of the century, the consumption of meat, processed food, and ultra-processed food has become popular. It is anticipated that these changes in the Japanese dietary environment will increase the risk of developing psychosomatic disorders., Methods: In this study, we examined the relationship between dietary habits, psychosomatic disorders, and a sense of achievement. For men and women aged 20-80 years ( n = 851) living in and around Ebetsu City, Hokkaido, Japan, a questionnaire on dietary habits over the past year, including mental and physical stress and a sense of achievement, was administered. The associations between dietary habits and psychosomatic disorders or a sense of achievement were analyzed using logistic regression ( n = 654)., Results: The associations between dietary habits and psychosomatic disorders differ depending on sex and age. We found that subjects who consumed more processed meat and ultra-processed food reported more psychosomatic disorders. On the other hand, those who perceived a sense of achievement consumed higher amounts of vegetables, albeit with a lower fish intake., Conclusions: In this study, we demonstrated that dietary habits and food ingredients are associated with mental and physical stress and a sense of achievement. Fish, which is considered to be good for the body, was mostly consumed by subjects who experienced mental and physical stress. These data indicate that highly stressful conditions may encourage fish consumption, as the body needs to mitigate psychosomatic disorders.

Background/objectives: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann's criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan., Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann's criteria were calculated by comparing diagnoses with those made by the JPDS Committee., Results: Of the 786 included cases, Hermann's criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann's criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as "definite" by both criteria., Conclusions: The findings suggest that Hermann's criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.

Although α-synuclein seed amplification assays (α-syn SAA) are promising, its sensitivity may be affected by heterogeneity among patients with Lewy body disease (LBD). We evaluated whether α-syn SAA sensitivity is affected by patient heterogeneity, using 123 I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in early drug-naïve patients. Thirty-four patients with clinically established or probable Parkinson's disease (PD) and seven with dementia with Lewy bodies (DLB) or prodromal DLB were included. While 85.2% of patients with abnormal cardiac MIBG were α-syn SAA positive, only 14.3% were positive among those with normal scans. Logistic regression analysis showed that MIBG positivity was the only significant variable associated with α-syn SAA positivity (odds ratio 74.2 [95% confidence interval 6.1-909]). Although α-syn SAA is sensitive for LBD in patients with abnormal MIBG, the sensitivity may be lower in those with normal MIBG. Further studies are necessary to evaluate the association between patient heterogeneity and α-syn SAA sensitivity., (© 2024. The Author(s).)

Background: Multidisciplinary discussion (MDD), in which physicians, radiologists, and pathologists communicate and diagnose together, has been reported to improve diagnostic accuracy compared to diagnoses made solely by physicians. However, even among experts, diagnostic concordance of MDD is not always good, and some patients may not receive a specific diagnosis due to insufficient findings. A provisional diagnosis based on the ontology with a diagnostic confidence level has recently been proposed. Additionally, we developed an artificial intelligence model to differentiate idiopathic pulmonary fibrosis (IPF) from other chronic interstitial lung diseases (ILD)s, which needs validation in a broader population., Methods: This prospective nationwide ILD registry has recruited patients with newly diagnosed ILD at the referral respiratory hospitals in Japan and provides rapid MDD diagnoses and treatment recommendations through a central online MDD platform with a 3-year follow-up period. A modified diagnostic ontology is used. If no diagnosis reaches more than 50% certainty, the diagnosis is unclassifiable ILD. If multiple diseases are expected, the diagnosis with a high probability takes precedence. If the confidence levels for the top two possible diagnoses are equal, the diagnosis can be unclassifiable. The registry uses tentative diagnostic criteria for nonspecific interstitial pneumonia with organising pneumonia and smoking-related ILD not otherwise specified as possible new entities. Central MDD diagnosticians review the clinical data, test results, radiology images, and pathological specimens on a dedicated website and conduct MDD diagnoses using online meetings with a cloud-based reporting system. This study aims to (1) provide MDD diagnoses with treatment recommendations; (2) determine the overall ILD rates in Japan; (3) clarify the reasons for unclassifiable ILDs; (4) evaluate possible new disease entities; (5) identify progressive phenotypes and create a clinical prediction model; (6) measure the agreement rate between institutional and central diagnoses in ILD referral and non-referral centres; (7) identify key factors for each specific ILD diagnosis; and (8) create a new disease classification system based on treatment strategies, including the use of antifibrotic drugs., Discussion: This study will provide ILD frequencies, including new entities, using central MDD on dedicated online systems, and develop a machine learning model for ILD diagnosis and prognosis prediction., Trial Registration: UMIN-CTR Clinical Trial Registry (UMIN000040678)., (© 2024. The Author(s).)

Introduction: Adiponectin (APN) is a multimeric protein with anti-inflammatory properties that is specifically secreted by adipocytes. Continuous plasma exchange with dialysis (cPED) is a blood purification therapy in which plasma exchange is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers., Methods: Patients with sepsis were divided into two groups based on the presence or absence of acute kidney injury (AKI) complications: AKI and non-AKI group., Results: Plasma APN levels significantly increased after cPED in both groups. The creatinine levels in the AKI group before cPED were significantly higher than those in the non- AKI group. The plasma APN levels in the AKI group before cPED were significantly higher than those in the non-AKI group., Conclusion: cPED increased APN levels in both patients with and without AKI. Therefore, cPED therapy may be a promising intervention for increasing APN levels in patients with sepsis., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Aim: Bear-related trauma is a significant concern in Japan. This study identified trauma patterns, outcomes, and therapeutic approaches for bear-related injuries treated., Methods: This retrospective observational study used medical records from Akita University Hospital, focusing on patients with bear-related trauma in 2023. Demographic data, injury details, treatment procedures, and outcomes were extracted., Results: The study included 20 patients (median age: 74.5 years, 65% males). Most injuries occurred in human habitats, mainly in autumn, with the face being the most affected area (90%). Three patients required emergency transfusions and tracheal intubation. Emergency surgery was performed in 52.6% of patients, and 42.1% were admitted to the intensive care unit. All patients survived with a median hospital stay of 17 days. However, 15.8% of patients had significant sequelae, such as blindness. Despite prophylactic antibiotics, wound infections occurred in 21.1% of patients, particularly in deep wounds that were not adequately washed under general anesthesia., Conclusions: Bear-related trauma often results in severe upper-body injuries that require prompt medical intervention. These findings highlight the need for improved preventive measures and strategies for initial treatment and long-term care., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

DNA rearrangements, including inversions, translocations, and large insertions/deletions (indels), are crucial for crop evolution, domestication, and improvement. The rearrangements are frequently induced by ion beams via the mis-repair of DNA double-strand breaks (DSBs). Unfortunately, how ion beam-induced DSBs are repaired has not been comprehensively analyzed and the mechanisms underlying DNA rearrangements remain unclear. In this study, clonal sectors originating from single mutated cells in carbon ion-irradiated plants were used for whole-genome sequencing analyses after Arabidopsis seeds and seedlings were irradiated. Comparative analyses of the induced mutations (e.g., size and frequency of indels and microhomology at the junctions of the rearrangements) in the irradiated materials suggested that the broken/rejoined DSB ends were more extensively processed in seedlings than in seeds. A mutation to canonical non-homologous end-joining (c-NHEJ), which is a DSB repair pathway with minimal processing of DSB ends, increased the sensitivity to ion beams more in the seeds than in the seedlings, which was consistent with the junction analysis results, indicative of the minor contribution of c-NHEJ to the carbon ion-induced DSB repair in seedlings. Considering the characteristics of the large templated insertions in irradiated seedlings, ion-beam-induced DSBs in seedlings are likely repaired primarily by a polymerase theta-mediated pathway. Polymerase theta-deficient seedlings were more sensitive to ion beams than the c-NHEJ-deficient seedlings, consistent with this hypothesis. This study revealed the key characteristics of ion beam-induced DSBs and the associated repair mechanisms related to the physiological status of the irradiated materials, with implications for elucidating the occurrence and induction of rearrangements., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Direct reinfusion of pericardial blood during cardiac surgery triggers a systemic inflammatory response. Although various inflammatory mediators have been identified as triggers, the role of damage-associated molecular patterns (DAMPs) remains poorly understood. Despite guidelines recommending against this practice owing to its harmful effects, it is sometimes used in emergencies., Case Presentation: A 72-year-old man with atrial fibrillation and cerebral infarction developed cardiac tamponade during catheter ablation. He underwent pericardial drainage and direct blood reinfusion. He was transferred to our ICU, where he developed acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). Despite aggressive management, the patient died 41 days after admission., Conclusion: This case highlights severe adverse events following direct reinfusion of pericardial blood. These findings suggest a significant role for DAMPs in mediating these inflammatory responses. Direct reinfusion of pericardial drainage blood should be avoided during emergencies to prevent life-threatening complications., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: Many patients who get discharged from the intensive care unit experience physical dysfunction that persists even after discharge. Physical dysfunction is associated with skeletal muscle atrophy and accompanying intensive care unit-acquired weakness in the early stages of intensive care unit admission, and early diagnosis and prevention with early mobilization are crucial. However, the amount of physical activity required for early mobilization remains controversial in critically ill patients. This study aims to reveal the optimal mobilization quantification score dose associated with physical dysfunction after hospital discharge., Methods: This is a multicenter prospective cohort study planned in 22 facilities; all consecutive patients admitted to the participating facilities between June 2024 and May 2025 will be included. Adult patients on ventilator management for at least 2 days and who will consent to this study will be included. Patients' mobility level and duration will be documented by the mobilization quantification score during their intensive care unit stay, and physical dysfunction will be assessed using muscle mass changes from day one to seven with ultrasonography and the Short-Form 12 Health Survey at 3 months after hospital discharge. The primary outcome is physical dysfunction at 3 months., Results and Conclusion: Mobilization quantification score dose and muscle mass evaluation with ultrasonography will enable the quantification of the early mobilization intervention. This study will lay the foundation for future randomised studies., Competing Interests: The authors declare no conflicts of interest in relation to the work presented in the manuscript., (© 2024 Society for Clinical Epidemiology.)

Biofertilizers are promising technologies for achieving sustainable agriculture. However, high-temperature tolerance is a constraint that limits the function of microbial inoculants. To characterize the genetic changes responsible for the high-temperature tolerance of rhizobia, mutant screening was performed using Bradyrhizobium diazoefficiens USDA110. The wild-type cells were mutagenized with carbon-ion irradiation, and two mutant strains, designated M10 and M14, were obtained after a three-day heat-shock treatment at 43 °C. In particular, M14 showed superior growth at 36 °C, at which temperature growth of the wild type was extremely slow, whereas M14 grew more slowly than the wild type at 32 °C. Whole-genome sequencing revealed that M10 had seven point mutations, whereas M14 had eight point mutations together with a 1.27 Mb inversion. RNA sequencing showed that the number of differentially expressed genes greatly exceeded the actual number of induced mutations. In M14, a gene cluster associated with pyruvate metabolism was markedly downregulated, probably because of disjunction with the promoter region after inversion, and was considered to be the cause of the slow growth rate of M14 at 32 °C. Notably, transmembrane proteins, including porins, were enriched among the genes upregulated in both M10 and M14. M14 was confirmed to retain symbiotic functions with soybeans. These results indicate that high-temperature tolerance was conferred by random mutagenesis while the symbiotic functions of rhizobia was maintained.

Background: Cancer initiation has long been "unknowable" in biology and medicine. In 1987, however, Moore and our research group observed single hepatocytes and minifoci that were strongly positive for glutathione S-transferase P-form (GST-P) in the rat liver as early as 2 to 3 days after initiation by diethylnitrosamine prior to the induction of GST-P + foci and nodules. The induction of GST-P + single hepatocytes, precursors of GST-P + foci and nodules, was considered genetic. But, the details of the induction mechanism have remained unclear despite various examinations over a long period., Methods: Male Sprague-Dawley rats (aged 6 weeks) were fed a basal diet containing either benzyl isothiocyanate (BITC, 0.5% by wt) or 2-acetylaminofluorene (AAF, 0.04%) ad libitum for appropriate time intervals. All animals were anesthetized and euthanized. The livers obtained were excised, cut into 3- to 4-mm-thick slices and fixed in cold acetone at 4 °C. The liver specimens were then sliced into 25-µm-thick sections in PBS using an automated microtome (Vibratome 1500 Sectioning System, Vibratome Products, NY, USA). Immunocytochemical staining was performed in free solution, and the results were examined via digital light microscopy (Coolscope, Nikon, Tokyo)., Results: 3D analysis using a vibratome showed that GST-P is rapidly excreted into the bile of the liver of animals in response to strong carcinogenic stress caused by promoters or initiators. "Rapid biliary excretion of GST-P" was widely and commonly observed in all hepatocytes, GST-P + single hepatocytes, minifoci, foci and nodules under appropriate conditions. Surprisingly, on the basis of these key findings, a new mechanism of cancer initiation involving the transformation of hepatocytes into GST-P + single hepatocytes and minifoci in animal livers was identified. In addition, the initiation process was determined to be nongenetic because mutation is an invisible rare event., Conclusions: This short review describes several details about breakthrough findings on cancer initiation in rat livers, the application of 3D analysis to other cancers and the importance in the genetic analysis in malignant diseases., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome., Methods: Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm., Results: The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes., Conclusion: Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: To report the surgical outcomes of a modified trabeculectomy technique involving implanting the Tenon's layer under the scleral flap., Design: Prospective, interventional case series., Participants: 51 eyes with medically uncontrolled glaucoma were enrolled for this study. A new trabeculectomy technique, the Tenon's filtration technique for trabeculectomy (TFT-LEC) was used in 26 eyes, while a conventional procedure, normal trabeculectomy (N-LEC), was used for 25 eyes., Methods: Intraocular pressure (IOP) control, the number of glaucoma medications, the need for additional interventions, and postoperative complications were assessed., Results: Twelve months postoperatively, the mean IOP was 13.5 ± 0.5 mmHg in the TFT-LEC group and 15.4 ± 0.5 mmHg in the N-LEC group (p = 0.13). The TFT-LEC group required an average of 1.3 ± 1.0 additional glaucoma medications (21 cases required only ripasudil) postoperatively, with no cases of bleb needling revision or reoperation. The N-LEC group required an average of 1.7 ± 1.5 glaucoma medications (p = 0.43) compared to TFT-LEC group, eight cases (32%) required bleb needling revision (p = 0.002), and one case (4%) of reoperation (p = 0.49). The complications in the TFT-LEC group included shallow anterior chamber in six (23 %) cases (p = 1.00) compared to N-LEC group, choroidal detachment in two (8%) cases (p = 0.42), and anterior chamber hemorrhage in seven (27%) cases (p = 0.29). None of these complications affected visual function., Conclusions: This new technique involving implanting the Tenon's layer under the scleral flap may improve the postoperative outcomes of trabeculectomy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This in vivo mouse model study was conducted to investigate the temporal alteration of the function of CD36 in salivary secretion. CD36 was highly expressed in the parotid gland of BALB/c mice. No significant variations were shown in the CD36 levels in the 8-, 48-, and 72-week-old animals. However, pilocarpine-induced salivary secretion was reduced in an age-dependent manner, showing a significantly low level at the age of 72 weeks. Pilocarpine-induced salivary secretion was significantly reduced by pretreatment with a CD36 inhibitor at 8 and 48 weeks, but not at 72 weeks. In senescence-accelerated mice (SAM), the pilocarpine-induced salivary secretion was significantly reduced at the age of 56 weeks, and a significantly lower amount of CD36 was demonstrated in the parotid gland, compared with the control. These results suggest that the involvement of parotid CD36 in mouse salivary secretion is altered with age., (© 2024. The Author(s).)

Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA., (© 2024. The Author(s).)

Although promoting healthy eating is a policy objective, the manageability of dietary habits remains uncertain. Personal dietary patterns reflect many factors, some of which are relatively manageable for individuals whilst others are not. In this article, assuming that some sort of information about the manageability of dietary habits is contained in the observed patterns of food consumption, we focused on dietary patterns on their own. We introduced a statistical descriptive model for data from a food frequency questionnaire, estimated the strength of pairwise linkage between foodstuffs, and grouped foodstuffs by applying community detection to the networks of the estimated inter-food linkages. Those linkages represent the co-movement of pairs of food in consumption. Furthermore, we demonstrated an analysis of the relationship between mental health and dietary habits, considering the aspect of the manageability of dietary habits. Using an observational study in Japan, we obtained the following results: 115 foodstuffs were divided into three groups for both genders, but the compositions were different by gender; in the analysis of mental and physical health, some stress response items were associated with a dependence on some of those food groupings (e.g., "extremely tired" was negatively associated with a group containing tomatoes, cucumber, mandarin, etc., for female subjects). As the grouping of foodstuffs based on our estimation depicted an internal structure of dietary habit that a healthy eating policy could regard as a constraint, it follows that we should design such a policy along the same lines as that grouping.

Background: Recently, the investigation of cerebrospinal fluid (CSF) biomarkers for diagnosing human prion diseases (HPD) has garnered significant attention. Reproducibility and accuracy are paramount in biomarker research, particularly in the measurement of total tau (T-tau) protein, which is a crucial diagnostic marker. Given the global impact of the coronavirus disease pandemic, the frequency of measuring this protein using one of the world's fully automated assays, chemiluminescent enzyme immunoassay (CLEA), has increased. At present, the diagnosis and monitoring of neurological diseases mainly rely on traditional methods, but their accuracy and responsiveness are limited. There is limited knowledge of the accuracy of CLEA in tau measurements. We aimed to measure T-tau protein using CLEA and to elucidate its merits and limitations., Methods: We randomly selected 60 patients with rapidly progressive dementia, using ELISA and CLEA analysis of cerebrospinal fluid specimens. Additionally, we used Western blotting to detect the presence of 14-3-3 protein and employed real-time quaking-induced conversion (RT-QuIC) assays to analyze the same set of samples. Furthermore, we examined the correlation coefficient between ELISA and CLEA results in a subset of 60 samples. Moreover, using CLEA, we evaluated the diurnal reproducibility, storage stability, dilutability, and freeze-thaw effects in three selected samples., Results: In 172 patients, 172 samples were extracted, with each patient providing only one sample, and a total of 88 (35 men and 53 women) tested positive for HPD in the RT-QuIC assay. In contrast, all CSF samples from the remaining 84 patients without HPD (50 men and 34 women) tested negative in the RT-QuIC assay. Both ELISA and CLEA showed perfect sensitivity and specificity (100%) in measuring T-tau protein levels. In addition, ELISA and CLEA are similar in terms of measurement sensitivity and marginal effect of detection extrema. CLEA analysis exhibited instability for certain samples with T-tau protein levels exceeding 2000 pg/mL, leading to low reproducibility during dilution analysis., Conclusions: Our findings indicate that CLEA outperforms ELISA in terms of diurnal reproducibility, storage stability, and freeze-thaw effects. However, ELISA demonstrated superior performance in the dilution assay. Therefore, it is imperative to develop innovative approaches for the dilution of biomarker samples for CLEA measurements during clinical trials.

The vertebral column is a characteristic structure of vertebrates. Genetic studies in mice have shown that Hox-mediated patterning plays a key role in specifying discrete anatomical regions of the vertebral column. Expression pattern analyses in several vertebrate embryos have provided correlative evidence that the anterior boundaries of Hox expression coincide with distinct anatomical vertebrae. However, because functional analyses have been limited to mice, it remains unclear which Hox genes actually function in vertebral patterning in other vertebrates. In this study, various zebrafish Hox mutants were generated for loss-of-function phenotypic analysis to functionally decipher the Hox code responsible for the zebrafish anterior vertebrae between the occipital and thoracic vertebrae. We found that Hox genes in HoxB- and HoxC-related clusters participate in regulating the morphology of the zebrafish anterior vertebrae. In addition, medaka hoxc6a was found to be responsible for anterior vertebral identity, as in zebrafish. Based on phenotypic similarities with Hoxc6 knockout mice, our results suggest that the Hox patterning system, including at least Hoxc6, may have been functionally established in the vertebral patterning of the common ancestor of ray-finned and lobe-finned fishes., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Purpose: This study aimed to elucidate the relationship between diurnal masseter muscle activity and awareness of diurnal awake bruxism (d-AB) by conducting a comparative analysis of electromyographic (EMG) data from individuals with and without awareness of diurnal awake bruxism (d-AB), utilizing EMG data gathered from multiple subjects., Methods: Unilateral masseter electromyography (EMG) recordings were performed during the daytime using an ultraminiature wearable EMG device. A total of 119 participants (59 with awareness of diurnal tooth clenching [d-TC] and 60 without awareness of d-TC) were included. Waveforms longer than 0.25 s with the two amplitude conditions, exceeding twice the baseline and >5% of maximum voluntary clenching, were extracted. In addition, the number of bursts and episodes (groups of bursts), burst duration, and burst peak amplitude were calculated for each participant., Results: There were no significant differences in the EMG parameters between the groups with and without awareness of d-TC. Additionally, the frequency distribution of the number of EMG waveforms exhibited wide ranges and substantial overlap between the two groups., Conclusions: The variability in the number of bursts and episodes, burst peak amplitude, and burst duration among subjects suggests the need for an objective classification of d-AB severity based on EMG values. The absence of significant differences and large overlap in frequency distributions between the groups with and without awareness of d-TC indicate difficulty in predicting muscle activity solely based on awareness of d-AB.

A novel method for the quantification of antifungal activity of fungicides and painted surfaces, mycelial invasion distance (MID) method, was developed and applied to the quantification of activities of parabens and an antifungal paint. In this method, the MID of aerial mycelia on a test paper or a panel placed on a nutrient agar plate was measured with a stereoscopic microscope and a micro-ruler. The antifungal activities of the parabens and painted surfaces were expressed as the MID. The higher the hydrophobicity of parabens, the longer the MID, that is the lower the antifungal activity, were observed. Conversely, relatively polar parabens, such as methyl and ethyl parabens, exhibited stronger antifungal activity, that is shorter MID. The most hydrophobic paraben, benzyl paraben, showed the weakest antifungal activity. Furthermore, it was confirmed that the MID method was effective for the evaluation of the painted surfaces., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Acute subdural hematoma (ASDH) is a life-threatening condition, and hematoma removal is necessary as a lifesaving procedure when the intracranial pressure is highly elevated. However, whether decompressive craniectomy (DC) or conventional craniotomy (CC) is adequate remains unclear. Hinge craniotomy (HC) is a technique that provides expansion potential for decompression while retaining the bone flap. At our institution, HC is the first-line operation instead of DC for traumatic ASDH, and we present the surgical outcomes., Methods: From January 1, 2017, to December 31, 2022, 372 patients with traumatic ASDH were admitted to our institution, among whom 48 underwent hematoma evacuation during the acute phase. HC was performed in cases where brain swelling was observed intraoperatively. If brain swelling was not observed, CC was selected. DC was performed only when the brain was too swollen to allow replacement of the bone flap. We conducted a retrospective analysis of patient demographics, prognosis, and subsequent cranial procedures for each technique., Results: Of the 48 patients, 2 underwent DC, 23 underwent HC, and 23 underwent CC. The overall mortality rate was 20.8% (10/48) at discharge and 30.0% (12/40) at 6 months. The in-hospital mortality rates for DC, HC, and CC were 100% (2/2), 21.7% (5/23), and 13.0% (3/23), respectively. Primary brain injury was the cause of death in five patients whose brainstem function was lost immediately after surgery. No fatalities were attributed to the progression of postoperative brain herniation. In only one case, the cerebral contusion worsened after the initial surgery, leading to brain herniation and necessitating secondary DC., Conclusions: The strategy of performing HC as the first-line operation for ASDH did not increase the mortality rate compared with past surgical reports and required secondary DC in only one case., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The dorsal and anal fins can vary widely in position and length along the anterior-posterior axis in teleost fishes. However, the molecular mechanisms underlying the diversification of these fins remain unknown. Here, we used genetic approaches in zebrafish and medaka, in which the relative positions of the dorsal and anal fins are opposite, to demonstrate the crucial role of hox genes in the patterning of the teleost posterior body, including the dorsal and anal fins. By the CRISPR-Cas9-induced frameshift mutations and positional cloning of spontaneous dorsalfinless medaka, we show that various hox mutants exhibit the absence of dorsal or anal fins, or a stepwise posterior extension of these fins, with vertebral abnormalities. Our results indicate that multiple hox genes, primarily from hoxc -related clusters, encompass the regions responsible for the dorsal and anal fin formation along the anterior-posterior axis. These results further suggest that shifts in the anterior boundaries of hox expression which vary among fish species, lead to diversification in the position and size of the dorsal and anal fins, similar to how modulations in Hox expression can alter the number of anatomically distinct vertebrae in tetrapods. Furthermore, we show that hox genes responsible for dorsal fin formation are different between zebrafish and medaka. Our results suggest that a novel mechanism has occurred during teleost evolution, in which the gene network responsible for fin formation might have switched to the regulation downstream of other hox genes, leading to the remarkable diversity in the dorsal fin position., Competing Interests: Competing interests statement:The authors declare no competing interest.

The efficacy of convolutional neural network (CNN)-enhanced electrocardiography (ECG) in detecting hypertrophic cardiomyopathy (HCM) and dilated HCM (dHCM) remains uncertain in real-world applications. This retrospective study analyzed data from 19,170 patients (including 140 HCM or dHCM) in the Shinken Database (2010-2017). We evaluated the sensitivity, positive predictive rate (PPR), and F1 score of CNN-enhanced ECG in a ''basic diagnosis'' model (total disease label) and a ''comprehensive diagnosis'' model (including disease subtypes). Using all-lead ECG in the "basic diagnosis" model, we observed a sensitivity of 76%, PPR of 2.9%, and F1 score of 0.056. These metrics improved in cases with a diagnostic probability of ≥ 0.9 and left ventricular hypertrophy (LVH) on ECG: 100% sensitivity, 8.6% PPR, and 0.158 F1 score. The ''comprehensive diagnosis'' model further enhanced these figures to 100%, 13.0%, and 0.230, respectively. Performance was broadly consistent across CNN models using different lead configurations, particularly when including leads viewing the lateral walls. While the precision of CNN models in detecting HCM or dHCM in real-world settings is initially low, it improves by targeting specific patient groups and integrating disease subtype models. The use of ECGs with fewer leads, especially those involving the lateral walls, appears comparably effective., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Cholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c-SRC, which are tumor-promoting genes. The FAXC/ANXA2/c-SRC complex forms in the mitochondria. FAXC enhances SRC-dependent ANXA2 phosphorylation at tyrosine-24, and the C-terminal amino acid residues (351-375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial-mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In Japan, many workers are exposed to chronic stress, sleep deprivation, and nutritional imbalance. They tend still to go to work when ill, leading to decreased work performance and productivity, which has become a major social problem. We conducted a human entry study with the aim of finding a link between these two factors and proposing an optimized diet, believing that a review of diet may lead to an improvement in labor productivity. In this study, we used subjective accomplishment (SA) as a measure of productivity. First, we compared nutrient intake between groups with high and low SA using data from a health survey of 1564 healthy male and female adults. Significant differences were found in the intake of 13 nutrients in males and 15 nutrients in females, including potassium, vitamin A, insoluble fiber, and biotin. Recommended daily intake of these nutrients was determined from survey data. Next, we designed test meals containing sufficient amounts of 17 nutrients and conducted a single-arm intervention study (registration code UMIN000047054) in Kameyama City, Mie Prefecture, Japan. Healthy working adults (males and females aged 20-79 years) were recruited and supplied with test meals, which were eaten once a day 5 days a week for 8 weeks. SA was significantly higher and daytime sleepiness (DS) was significantly lower after lunch on workdays in younger participants (under 60 years) when they ate the test meals as breakfast or lunch. Our results suggest that SA and DS, which change daily, are strongly influenced by the meal eaten before work, and that taking the 17 nutrients may help prevent presenteeism and improve labor productivity.

Cryptococcus neoformans and Cryptococcus gattii cause cryptococcosis, a systemic mycosis that infects a wide range of species. Recent molecular biological investigations have allowed for the genotyping of these species, providing more detailed information on their pathogenicity and infection routes. Koalas ( Phascolarctos cinereus ) are frequently colonized by Cryptococcus spp., but molecular epidemiological studies have yet to be conducted in Japan. Here, we conducted multi-locus sequence typing (MLST) analysis on Cryptococcus spp. colonization isolates obtained from all koalas kept in seven parks across Japan. Out of 46 koalas examined, 10 (22%) were positive for C. gattii and 3 (6.5%) were positive for C. neoformans . All C. gattii isolates belonged to molecular type VGI and were either sequence type (ST) 51 or a novel ST, and all C. neoformans isolates belonged to molecular type VNI and ST23. Despite the frequent movement of koalas between parks, the STs were relatively park-specific, suggesting that the floor of the rearing barns is a source of infection and may act as a reservoir. MLST analysis confirmed that C. gattii was transported, established, and spread by koalas in areas where C. gattii was not originally present. MLST analysis is considered useful in assessing the pathogenicity and tracing the transmission routes of Cryptococcus spp. carried by koalas.IMPORTANCEThis is the first study to conduct a multi-locus sequence typing analysis on Cryptococcus spp. carried by captive koalas in Japan. Cryptococcosis remains a globally high-fatality fungal infection in humans, and captive koalas are known to carry a high percentage of Cryptococcus spp. Through this research, the molecular types and transmission routes of Cryptococcus spp. carried by koalas have been elucidated, revealing the potential role of enclosure flooring as a reservoir. It has been confirmed that Cryptococcus gattii , which is not endemic in Japan, has become established through koalas and is spreading to new individuals in Japan. This study is believed to provide valuable insights into koala conservation and contribute to the One Health approach for Cryptococcosis, a zoonotic infection., Competing Interests: The authors declare no conflict of interest.

Background: The potential of utilizing artificial intelligence with electrocardiography (ECG) for initial screening of aortic dissection (AD) is promising. However, achieving a high positive predictive rate (PPR) remains challenging., Methods and Results: This retrospective analysis of a single-center, prospective cohort study (Shinken Database 2010-2017, N = 19,170) used digital 12-lead ECGs from initial patient visits. We assessed a convolutional neural network (CNN) model's performance for AD detection with eight-lead (I, II, and V1-6), single-lead, and double-lead (I, II) ECGs via five-fold cross-validation. The mean age was 63.5 ± 12.5 years for the AD group (n = 147) and 58.1 ± 15.7 years for the non-AD group (n = 19,023). The CNN model achieved an area under the curve (AUC) of 0.936 (standard deviation [SD]: 0.023) for AD detection with eight-lead ECGs. In the entire cohort, the PPR was 7 %, with 126 out of 147 AD cases correctly diagnosed (sensitivity 86 %). When applied to patients with D-dimer levels ≥1 μg/dL and a history of hypertension, the PPR increased to 35 %, with 113 AD cases correctly identified (sensitivity 86 %). The single V1 lead displayed the highest diagnostic performance (AUC: 0.933, SD: 0.03), with PPR improvement from 8 % to 38 % within the same population., Conclusions: Our CNN model using ECG data for AD detection achieved an over 30% PPR when applied to patients with elevated D-dimer levels and hypertension history while maintaining sensitivity. A similar level of performance was observed with a single-lead V1 ECG in the CNN model., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Suzuki has received lecture fees from Daiichi Sankyo and Bristol-Myers Squibb. Dr. Yamashita has received research funding and/or lecture fees from Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb, Pfizer, Nippon Boehringer Ingelheim, Ono Pharmaceutical, and Toa Eiyo. J Motogi, T Umemoto, W Matsuzawa, T Takayanagi, A Hyodo, and K Satoh are employee at Nihon Kohden Corporation., (© 2024 The Authors.)

Background: Human prion diseases (HPDs) are fatal neurodegenerative disorders characterized by abnormal prion proteins (PrPSc). However, the detection of prion seeding activity in patients with high sensitivity remains challenging. Even though real-time quaking-induced conversion (RT-QuIC) assay is suitable for detecting prion seeding activity in a variety of specimens, it shows lower accuracy when whole blood, blood plasma, and blood-contaminated tissue samples are used. In this study, we developed a novel technology for the in vitro amplification of abnormal prion proteins in HPD to the end of enabling their detection with high sensitivity known as the enhanced quaking-induced conversion (eQuIC) assay., Methods: Three antibodies were used to develop the novel eQUIC method. Thereafter, SD50 seed activity was analyzed using brain tissue samples from patients with prion disease using the conventional RT-QUIC assay and the novel eQUIC assay. In addition, blood samples from six patients with solitary prion disease were analyzed using the novel eQuIC assay., Results: The eQuIC assay, involving the use of three types of human monoclonal antibodies, showed approximately 1000-fold higher sensitivity than the original RT-QuIC assay. However, when this assay was used to analyze blood samples from six patients with sporadic human prion disease, no prion activity was detected., Conclusion: The detection of prion seeding activity in blood samples from patients with sporadic prion disease remains challenging. Thus, the development of alternative methods other than RT-QuIC and eQuIC will be necessary for future research., (© 2024. The Author(s).)

This study examined the thermal dehydration characteristics of CaSO 4 ∙2H 2 O in a constant-volume rotary vessel. The experiment used CaSO 4 ∙2H 2 O particles obtained from the crushed waste gypsum board. The particle size ranged from 850 to 2000 μm, and the experiment was carried out at varying rotation speeds of 1, 10, and 35 rpm, with the vessel temperature heated to 180 °C. Temperature and pressure inside the vessel were measured simultaneously using the thermocouple and the pressure sensor. The XRPD measurement analyzed the transition of CaSO 4 ∙2H 2 O after the heating of particles. The result showed that the temperature growth rate was similar for high rotation speeds of 10 and 35 rpm, while periodic temperature changes occurred at the low rotation speed of 1 rpm. A distinguishing flow pattern was observed at the low rotation speed, and the particles inside the vessel collapsed periodically downward. This particle behavior was related to the temperature distribution of the rotation speed of 1 rpm. Additionally, the pressure in the vessel increased rapidly at higher rotation speeds. This trend indicates the desorption of the crystal water of CaSO 4 ∙2H 2 O due to the increasing temperature in the case of high rotation speed. Also, the XRPD measurement results showed the appearance of CaSO 4 ∙0.5H 2 O under the higher rotation speed conditions, and the mass fraction of CaSO 4 ∙0.5H 2 O increased with the rotation speed. Overall, the present study suggests that rotation speed plays a crucial role in determining the heat conduction and heat transfer of particles in a constant-volume rotary vessel.

Aim: The study aimed to investigate the association of vitality, as measured using the vitality index (Vix), with the survival outcomes of older adults with mild cognitive impairment (MCI) or dementia., Methods: We analyzed data from 3731 patients in the National Center for Geriatrics and Gerontology - Life Stories of Individuals with Dementia cohort from July 2010 to September 2018. The main focus was to correlate Vix scores with the time from the initial visit to death. Vix was categorized into "moderately to severely impaired" (0-7 points), "mildly impaired" (8-9 points), and "normal" (10 points) groups. Survival outcomes were assessed using a Cox proportional hazards model, adjusted for various factors. We conducted a mediation analysis to evaluate the effect of body mass index (BMI), instrumental activities of daily living (IADL), and basic activities of daily living (BADL) on the association between vitality and mortality. Stratified analysis was also conducted for the Mini-Mental State Examination groups., Results: We included 2740 patients with an average follow-up of 1315 days. The mortality rate was 15.7%. The Vix distribution was 16% at 0-7 points; 40%, 8-9 points; and 44%, 10 points. Patients in the "moderately to severely impaired" category, characterized by lower Vix scores, exhibited notably higher mortality rates. Mediation effects emphasized the significant roles of BMI, IADL, and BADL in influencing survival outcomes., Conclusions: Vitality significantly influences patient survival rates. The association between vitality and mortality seems to be mediated by IADL and BADL, which has significant clinical implications. Geriatr Gerontol Int 2024; 24: 221-228., (© 2024 Japan Geriatrics Society.)